{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T21:53:33Z","timestamp":1791582813797,"version":"4.3.4"},"reference-count":80,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2022,2,16]],"date-time":"2022-02-16T00:00:00Z","timestamp":1644969600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005981","name":"Direktorat Jenderal Pendidikan Tinggi","doi-asserted-by":"publisher","award":["3340\/E4.4\/K\/2014"],"award-info":[{"award-number":["3340\/E4.4\/K\/2014"]}],"id":[{"id":"10.13039\/501100005981","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Biofilm-associated infections with<jats:italic>Staphylococcus aureus<\/jats:italic>are difficult to treat even after administration of antibiotics that according to the standard susceptibility assays are effective. Currently, the assays used in the clinical laboratories to determine the sensitivity of<jats:italic>S<\/jats:italic>.<jats:italic>aureus<\/jats:italic>towards antibiotics are not representing the behaviour of biofilm-associated<jats:italic>S<\/jats:italic>.<jats:italic>aureus<\/jats:italic>, since these assays are performed on planktonic bacteria. In research settings, microcalorimetry has been used for antibiotic susceptibility studies. Therefore, in this study we investigated if we can use isothermal microcalorimetry to monitor the response of biofilm towards antibiotic treatment in real-time. We developed a reproducible method to generate biofilm in an isothermal microcalorimeter setup. Using this system, the sensitivity of 5 methicillin-sensitive<jats:italic>S<\/jats:italic>.<jats:italic>aureus<\/jats:italic>(MSSA) and 5 methicillin-resistant<jats:italic>S<\/jats:italic>.<jats:italic>aureus<\/jats:italic>(MRSA) strains from different genetic lineages were determined towards: flucloxacillin, cefuroxime, cefotaxime, gentamicin, rifampicin, vancomycin, levofloxacin, clindamycin, erythromycin, linezolid, fusidic acid, co-trimoxazole, and doxycycline. In contrast to conventional assays, our calorimetry-based biofilm susceptibility assay showed that<jats:italic>S<\/jats:italic>.<jats:italic>aureus<\/jats:italic>biofilms, regardless MSSA or MRSA, can survive the exposure to the maximum serum concentration of all tested antibiotics. The only treatment with a single antibiotic showing a significant reduction in biofilm survival was rifampicin, yet in 20% of the strains, emerging antibiotic resistance was observed. Furthermore, the combination of rifampicin with flucloxacillin, vancomycin or levofloxacin was able to prevent<jats:italic>S<\/jats:italic>.<jats:italic>aureus<\/jats:italic>biofilm from becoming resistant to rifampicin. Isothermal microcalorimetry allows real-time monitoring of the sensitivity of<jats:italic>S<\/jats:italic>.<jats:italic>aureus<\/jats:italic>biofilms towards antibiotics in a fast and reliable way.<\/jats:p>","DOI":"10.1371\/journal.pone.0260272","type":"journal-article","created":{"date-parts":[[2022,2,16]],"date-time":"2022-02-16T18:40:39Z","timestamp":1645036839000},"page":"e0260272","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":26,"title":["Real time monitoring of Staphylococcus aureus biofilm sensitivity towards antibiotics with isothermal microcalorimetry"],"prefix":"10.1371","volume":"17","author":[{"given":"Andi Rofian","family":"Sultan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehri","family":"Tavakol","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole A.","family":"Lemmens-den Toom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter D.","family":"Croughs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nelianne J.","family":"Verkaik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annelies","family":"Verbon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Willem J. 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bacterial arthritis","volume":"54","author":"MA Cimmino","year":"1997","journal-title":"Drugs"},{"issue":"4","key":"pone.0260272.ref004","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1097\/00002281-199108000-00013","article-title":"Infected arthroplasties","volume":"3","author":"AC Ross","year":"1991","journal-title":"Curr Opin Rheumatol"},{"issue":"1","key":"pone.0260272.ref005","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1302\/2058-5241.2.160027","article-title":"Paediatric bone and joint infection","volume":"2","author":"AD Iliadis","year":"2017","journal-title":"EFORT Open Rev"},{"issue":"2","key":"pone.0260272.ref006","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1089\/sur.2016.165","article-title":"Methicillin-Resistant Staphylococcus aureus in Foot Osteomyelitis","volume":"18","author":"CN Ashong","year":"2017","journal-title":"Surg Infect (Larchmt)."},{"issue":"4","key":"pone.0260272.ref007","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.1002\/jor.23723","article-title":"Targeting intracellular Staphylococcus aureus to lower recurrence of orthopaedic infection","volume":"36","author":"DH Dusane","year":"2018","journal-title":"J Orthop Res"},{"issue":"9","key":"pone.0260272.ref008","doi-asserted-by":"crossref","first-page":"1955","DOI":"10.1093\/jac\/dkq257","article-title":"Penetration of antibiotics through Staphylococcus aureus and Staphylococcus epidermidis biofilms","volume":"65","author":"R Singh","year":"2010","journal-title":"J Antimicrob Chemother"},{"issue":"9276","key":"pone.0260272.ref009","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/S0140-6736(01)05321-1","article-title":"Antibiotic resistance of bacteria in biofilms","volume":"358","author":"PS Stewart","year":"2001","journal-title":"Lancet"},{"issue":"2","key":"pone.0260272.ref010","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1111\/j.1574-6968.2004.tb09643.x","article-title":"What drives bacteria to produce a biofilm?","volume":"236","author":"KK Jefferson","year":"2004","journal-title":"FEMS Microbiol Lett"},{"key":"pone.0260272.ref011","article-title":"During the Early Stages of Staphylococcus aureus Biofilm Formation, induced Neutrophil Extracellular Traps (NETs) are degraded by Autologous Thermonuclease","author":"AR Sultan","year":"2019","journal-title":"Infect Immun"},{"issue":"8","key":"pone.0260272.ref012","doi-asserted-by":"crossref","DOI":"10.1128\/IAI.00352-18","article-title":"Production of Staphylococcal Complement Inhibitor (SCIN) and Other Immune Modulators during the Early Stages of Staphylococcus aureus Biofilm Formation in a Mammalian Cell Culture Medium","volume":"86","author":"AR Sultan","year":"2018","journal-title":"Infect 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Microbiol"},{"issue":"5","key":"pone.0260272.ref016","doi-asserted-by":"crossref","first-page":"3007","DOI":"10.1128\/IAI.73.5.3007-3017.2005","article-title":"Extracellular carbohydrate-containing polymers of a model biofilm-producing strain, Staphylococcus epidermidis RP62A","volume":"73","author":"I Sadovskaya","year":"2005","journal-title":"Infect Immun"},{"issue":"3","key":"pone.0260272.ref017","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1128\/JB.01222-08","article-title":"Protein A-mediated multicellular behavior in Staphylococcus aureus","volume":"191","author":"N Merino","year":"2009","journal-title":"J Bacteriol"},{"issue":"9","key":"pone.0260272.ref018","doi-asserted-by":"crossref","first-page":"824","DOI":"10.5301\/ijao.5000051","article-title":"Extracellular DNA in biofilms","volume":"34","author":"L Montanaro","year":"2011","journal-title":"Int J Artif Organs"},{"issue":"19","key":"pone.0260272.ref019","doi-asserted-by":"crossref","first-page":"8113","DOI":"10.1073\/pnas.0610226104","article-title":"The cidA murein hydrolase regulator contributes to DNA release and biofilm development in Staphylococcus aureus","volume":"104","author":"KC Rice","year":"2007","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"5559","key":"pone.0260272.ref020","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.1126\/science.295.5559.1487","article-title":"Extracellular DNA required for bacterial biofilm formation","volume":"295","author":"CB Whitchurch","year":"2002","journal-title":"Science"},{"issue":"11","key":"pone.0260272.ref021","doi-asserted-by":"crossref","first-page":"3055","DOI":"10.1016\/j.bbamem.2015.02.009","article-title":"Mechanisms of resistance to antimicrobial peptides in staphylococci","volume":"1848","author":"HS Joo","year":"2015","journal-title":"Bba-Biomembranes"},{"issue":"7562","key":"pone.0260272.ref022","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1136\/bmj.38834.421713.2F","article-title":"Mortality after Staphylococcus aureus bacteraemia in two hospitals in Oxfordshire, 1997\u20132003: cohort study","volume":"333","author":"DH Wyllie","year":"2006","journal-title":"BMJ"},{"issue":"3","key":"pone.0260272.ref023","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1128\/CMR.00134-14","article-title":"Staphylococcus aureus infections: epidemiology, pathophysiology, clinical manifestations, and management","volume":"28","author":"SY Tong","year":"2015","journal-title":"Clin Microbiol Rev"},{"issue":"5","key":"pone.0260272.ref024","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1093\/clinids\/9.5.891","article-title":"Prospective study of 114 consecutive episodes of Staphylococcus aureus bacteremia","volume":"9","author":"JM Mylotte","year":"1987","journal-title":"Rev Infect Dis"},{"issue":"11","key":"pone.0260272.ref025","doi-asserted-by":"crossref","DOI":"10.1007\/s11908-017-0599-0","article-title":"Once-Daily Treatments for Methicillin-Susceptible Staphylococcus aureus Bacteremia: Are They Good Enough?","volume":"19","author":"SA Lother","year":"2017","journal-title":"Curr Infect Dis Rep"},{"issue":"4","key":"pone.0260272.ref026","doi-asserted-by":"crossref","first-page":"e94690","DOI":"10.1371\/journal.pone.0094690","article-title":"Phenotypic resistance and the dynamics of bacterial escape from phage control.","volume":"9","author":"JJ Bull","year":"2014","journal-title":"PLoS One."},{"issue":"4","key":"pone.0260272.ref027","doi-asserted-by":"crossref","DOI":"10.1128\/JCM.01329-17","article-title":"Multicenter Evaluation of the Accelerate PhenoTest BC Kit for Rapid Identification and Phenotypic Antimicrobial Susceptibility Testing Using Morphokinetic Cellular Analysis","volume":"56","author":"P Pancholi","year":"2018","journal-title":"Journal of Clinical Microbiology"},{"issue":"2","key":"pone.0260272.ref028","doi-asserted-by":"crossref","first-page":"237","DOI":"10.3390\/antibiotics2020237","article-title":"Phenotypic Resistance to Antibiotics","volume":"2","author":"F Corona","year":"2013","journal-title":"Antibiotics (Basel)."},{"key":"pone.0260272.ref029","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1146\/annurev.micro.112408.134306","article-title":"Persister cells","volume":"64","author":"K. Lewis","year":"2010","journal-title":"Annu Rev Microbiol"},{"issue":"1","key":"pone.0260272.ref030","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1038\/nrmicro1557","article-title":"Persister cells, dormancy and infectious disease","volume":"5","author":"K. Lewis","year":"2007","journal-title":"Nat Rev Microbiol"},{"issue":"2","key":"pone.0260272.ref031","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1128\/CMR.15.2.167-193.2002","article-title":"Biofilms: survival mechanisms of clinically relevant microorganisms","volume":"15","author":"RM Donlan","year":"2002","journal-title":"Clin Microbiol Rev"},{"issue":"10","key":"pone.0260272.ref032","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1111\/1469-0691.12651","article-title":"Antimicrobial susceptibility testing in biofilm-growing bacteria","volume":"20","author":"MD Macia","year":"2014","journal-title":"Clin Microbiol Infect"},{"issue":"4","key":"pone.0260272.ref033","article-title":"Quantitative and Qualitative Assessment Methods for Biofilm Growth: A Mini-review.","volume":"6","author":"C Wilson","year":"2017","journal-title":"Res Rev J Eng Technol."},{"issue":"2","key":"pone.0260272.ref034","doi-asserted-by":"crossref","DOI":"10.3390\/biom8020029","article-title":"Critical Assessment of Methods to Quantify Biofilm Growth and Evaluate Antibiofilm Activity of Host Defence Peptides","volume":"8","author":"EF Haney","year":"2018","journal-title":"Biomolecules"},{"issue":"3","key":"pone.0260272.ref035","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1080\/1040841X.2016.1208146","article-title":"Critical review on biofilm methods","volume":"43","author":"J Azeredo","year":"2017","journal-title":"Crit Rev Microbiol"},{"issue":"1","key":"pone.0260272.ref036","doi-asserted-by":"crossref","first-page":"13040","DOI":"10.1038\/s41598-018-31437-y","article-title":"A steam-based method to investigate biofilm","volume":"8","author":"J Tasse","year":"2018","journal-title":"Sci Rep"},{"issue":"6","key":"pone.0260272.ref037","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1016\/j.cmi.2018.01.003","article-title":"Should standardized susceptibility testing for microbial biofilms be introduced in clinical practice?","volume":"24","author":"T Coenye","year":"2018","journal-title":"Clin Microbiol Infect"},{"key":"pone.0260272.ref038","first-page":"CD009528","article-title":"Standard versus biofilm antimicrobial susceptibility testing to guide antibiotic therapy in cystic fibrosis","volume":"10","author":"V Waters","year":"2017","journal-title":"Cochrane Database Syst Rev"},{"issue":"4","key":"pone.0260272.ref039","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1093\/jac\/dkl013","article-title":"Measurement of ampicillin, vancomycin, linezolid and gentamicin activity against enterococcal biofilms","volume":"57","author":"JA Sandoe","year":"2006","journal-title":"J Antimicrob Chemother"},{"issue":"1","key":"pone.0260272.ref040","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1128\/AAC.00583-09","article-title":"Chip calorimetry for fast and reliable evaluation of bactericidal and bacteriostatic treatments of biofilms","volume":"54","author":"F Buchholz","year":"2010","journal-title":"Antimicrob Agents Chemother"},{"issue":"3","key":"pone.0260272.ref041","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.ijmm.2012.12.009","article-title":"Chip-calorimetric monitoring of biofilm eradication with antibiotics provides mechanistic information","volume":"303","author":"F Mariana","year":"2013","journal-title":"Int J Med Microbiol"},{"key":"pone.0260272.ref042","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1007\/978-1-4939-0467-9_19","article-title":"Chip calorimetry for evaluation of biofilm treatment with biocides, antibiotics, and biological agents","volume":"1147","author":"FM Morais","year":"2014","journal-title":"Methods Mol Biol"},{"issue":"1\u20132","key":"pone.0260272.ref043","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.tca.2008.08.007","article-title":"Nano-calorimetry of small-sized biological samples","volume":"477","author":"J Lerchner","year":"2008","journal-title":"Thermochim Acta"},{"issue":"1","key":"pone.0260272.ref044","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1128\/CMR.00034-09","article-title":"Rifampin combination therapy for nonmycobacterial infections","volume":"23","author":"GN Forrest","year":"2010","journal-title":"Clin Microbiol Rev"},{"issue":"Suppl 1","key":"pone.0260272.ref045","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1016\/j.cmi.2014.10.024","article-title":"ESCMID guideline for the diagnosis and treatment of biofilm infections 2014","volume":"21","author":"N Hoiby","year":"2015","journal-title":"Clin Microbiol Infect"},{"issue":"7","key":"pone.0260272.ref046","doi-asserted-by":"crossref","first-page":"1455","DOI":"10.1093\/jac\/dkt072","article-title":"Antibiotic activity against small-colony variants of Staphylococcus aureus: review of in vitro, animal and clinical data","volume":"68","author":"LG Garcia","year":"2013","journal-title":"J Antimicrob Chemother"},{"issue":"Pt 8","key":"pone.0260272.ref047","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1099\/jmm.0.009720-0","article-title":"Role of persisters and small-colony variants in antibiotic resistance of planktonic and biofilm-associated Staphylococcus aureus: an in vitro study","volume":"58","author":"R Singh","year":"2009","journal-title":"J Med Microbiol"},{"issue":"10","key":"pone.0260272.ref048","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1038\/nrd4000","article-title":"Applying insights from biofilm biology to drug development\u2014can a new approach be developed?","volume":"12","author":"T Bjarnsholt","year":"2013","journal-title":"Nat Rev Drug Discov"},{"issue":"4","key":"pone.0260272.ref049","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1016\/j.ijantimicag.2009.12.011","article-title":"Antibiotic resistance of bacterial biofilms","volume":"35","author":"N Hoiby","year":"2010","journal-title":"Int J Antimicrob Agents"},{"issue":"2","key":"pone.0260272.ref050","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.tim.2016.09.009","article-title":"Architecture of a Species: Phylogenomics of Staphylococcus aureus","volume":"25","author":"PJ Planet","year":"2017","journal-title":"Trends Microbiol"},{"issue":"5","key":"pone.0260272.ref051","doi-asserted-by":"crossref","first-page":"2882","DOI":"10.1128\/jb.171.5.2882-2885.1989","article-title":"Expression and Inducibility in Staphylococcus-Aureus of the Meca Gene, Which Encodes a Methicillin-Resistant S Aureus Specific Penicillin-Binding Protein","volume":"171","author":"K Ubukata","year":"1989","journal-title":"Journal of Bacteriology"},{"issue":"2","key":"pone.0260272.ref052","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1016\/j.diagmicrobio.2009.08.021","article-title":"Genotypes, superantigen gene profiles, and presence of exfoliative toxin genes in clinical methicillin-susceptible Staphylococcus aureus isolates","volume":"66","author":"MJ van Trijp","year":"2010","journal-title":"Diagn Microbiol Infect Dis"},{"issue":"7","key":"pone.0260272.ref053","doi-asserted-by":"crossref","first-page":"1196","DOI":"10.1086\/444427","article-title":"Associations between Staphylococcus aureus Genotype, Infection, and In-Hospital Mortality: A Nested Case-Control Study","volume":"192","author":"HF Wertheim","year":"2005","journal-title":"J Infect Dis"},{"issue":"9320","key":"pone.0260272.ref054","doi-asserted-by":"crossref","first-page":"1819","DOI":"10.1016\/S0140-6736(02)08713-5","article-title":"Genome and virulence determinants of high virulence 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inoculation","volume":"7","author":"BC Slingerland","year":"2012","journal-title":"PLoS One"},{"issue":"24","key":"pone.0260272.ref058","doi-asserted-by":"crossref","first-page":"8845","DOI":"10.1128\/AEM.02398-12","article-title":"Staphylococcus aureus CC398 clade associated with human-to-human transmission","volume":"78","author":"AJ McCarthy","year":"2012","journal-title":"Appl Environ Microbiol"},{"issue":"1","key":"pone.0260272.ref059","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1093\/jac\/43.1.113","article-title":"The clinical efficacy of continuous-infusion flucloxacillin in serious staphylococcal sepsis","volume":"43","author":"K Leder","year":"1999","journal-title":"J Antimicrob Chemother"},{"issue":"10","key":"pone.0260272.ref060","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1097\/00006454-199710000-00011","article-title":"Concentration of cefuroxime in middle ear effusion of children with acute otitis media","volume":"16","author":"E Thoroddsen","year":"1997","journal-title":"Pediatr Infect Dis J"},{"issue":"Suppl 1","key":"pone.0260272.ref061","doi-asserted-by":"crossref","first-page":"S43","DOI":"10.1007\/BF01644217","article-title":"Studies of cefotaxime serum concentrations during surgery under general anaesthesia and its passage to the wound fluid after surgery for breast cancer","volume":"13","author":"T Ueda","year":"1985","journal-title":"Infection"},{"issue":"3","key":"pone.0260272.ref062","doi-asserted-by":"crossref","first-page":"202","DOI":"10.2165\/00003088-197803030-00002","article-title":"Why monitor serum levels of gentamicin?","volume":"3","author":"M Barza","year":"1978","journal-title":"Clin Pharmacokinet"},{"issue":"5","key":"pone.0260272.ref063","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1111\/j.1365-2125.1976.tb00644.x","article-title":"Serum concentrations and bioavailability of rifampicin and isoniazid in combination","volume":"3","author":"JC Garnham","year":"1976","journal-title":"Br J Clin Pharmacol"},{"issue":"1","key":"pone.0260272.ref064","first-page":"21","article-title":"Therapeutic monitoring of vancomycin in adult patients: a consensus review of the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society Of Infectious Diseases Pharmacists","volume":"31","author":"JH Martin","year":"2010","journal-title":"Clin Biochem Rev"},{"issue":"2","key":"pone.0260272.ref065","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1093\/jac\/dgk056","article-title":"Tissue and serum concentrations of levofloxacin 500 mg administered intravenously or orally for antibiotic prophylaxis in biliary surgery","volume":"51","author":"S Swoboda","year":"2003","journal-title":"J Antimicrob Chemother"},{"issue":"2","key":"pone.0260272.ref066","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1128\/AAC.8.2.220","article-title":"Concentration of clindamycin in human bone","volume":"8","author":"P Nicholas","year":"1975","journal-title":"Antimicrob Agents Chemother"},{"issue":"628","key":"pone.0260272.ref067","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1136\/pgmj.54.628.68","article-title":"Plasma concentration\/time curve of erythromycin after a 12-hour intravenous infusion of erythromycin lactobionate in man","volume":"54","author":"RL Parsons","year":"1978","journal-title":"Postgrad Med J"},{"issue":"11","key":"pone.0260272.ref068","doi-asserted-by":"crossref","first-page":"4605","DOI":"10.1128\/AAC.00177-10","article-title":"Therapeutic drug monitoring of linezolid: a retrospective monocentric analysis","volume":"54","author":"F Pea","year":"2010","journal-title":"Antimicrob Agents Chemother"},{"issue":"6","key":"pone.0260272.ref069","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1111\/j.1365-2133.1992.tb00105.x","article-title":"Levels of fusidic acid in skin blister fluid and serum after repeated administration of two 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